A Look at Preliminary Data of Final Phase 3 Trial: Sanofi's Dengue Vaccine Candidate
This blog post was originally published by the Dengue Vaccine Initiative (DVI). Please click here for DVI's full statement.
On Wednesday, Sanofi Pasteur published a press release with preliminary results of the second arm of the Phase 3 trial of its candidate dengue vaccine. The trial was conducted in Brazil, Colombia, Honduras, Mexico and Puerto Rico and involved 20,875 children and teenagers aged 9 to 16.
The announcement follows a series of updates made through the year about a previous similar, though smaller in size, Phase 3 trial conducted in Indonesia, Malaysia, the Philippines, Thailand and Vietnam, with 10,275 children and teenagers aged 2 to 14. A little less than two months ago, on July 10th, Capeding et al published a manuscript in The Lancet with the detailed Asia findings and a discussion followed by a commentary by Dr. Anneilies Wilder-Smith.
With this update, the dengue research community again awaits with anticipation the publication of the full results, which would move us closer to assessing the public health utility of this vaccine candidate and its potential in reducing the burden of dengue.
Wednesday’s data prelease indicates that the trial showed efficacy of 60.8 percent of reduction of dengue disease cases. Sanofi also announced that efficacy in this trial in Latin America was demonstrated for all serotypes, with 50.3 percent for serotype 1, 42.3 percent for serotype 2, 74.0 percent for serotype 3, and 77.7 percent for serotype 4.
The study conducted in Asia showed a lower efficacy of 56.5 percent against any virologically-confirmed dengue and efficacy against serotypes 1, 2, 3 and 4, of 50 percent, 35 percent, 78.4 percent and 75.3 percent, respectively. In Asia, vaccine efficacy was not statistically significant for serotype 2.
The Latin American trial remained consistent with previous trials of this candidate in that no safety concerns were observed. Sanofi also reported a significant reduction of the risk of hospitalization by 80.3 percent in Latin America, remaining consistent with a similar observation made in the Asian trial, where results showed a reduction by 67.2 percent.
What Does this Mean?
The data prerelease provides an insight into the Latin American Phase 3 trial. The results confirm the feasibility of protection against dengue by vaccination, including severe disease. However, the detailed data are required in order to fully assess the benefits and limitations of this vaccine candidate in preventing and controlling dengue. These full results will also allow for in depth examination to better understand the heterogeneities in vaccine performance in the two arms of Sanofi’s Phase 3 trial.
For example, why is the protection against serotype 2 low, both in the Asian and Latin American trials? Is the difference in age groups between both trials important in explaining the results of the efficacy of the vaccine, especially in relation to serotype 2? How do regional differences affect the analysis of viewing this data together?
Without the complete set of results, comparisons will not be exhaustive. Questions still remain, but as the last stage of this Phase 3 clinical trial, we are closer to deepening our knowledge on dengue vaccines and uncovering future challenges and their potential solutions.
Once the complete data are publicly available this year in November, as stated by Sanofi, the World Health Organization (WHO) will provide an independent assessment, as done for the Phase 3 study in Asia. Following licensure by a functional National Regulatory Authority (NRA), the WHO Strategic Advisory Group of Experts (SAGE) on immunization will advise WHO on the public health utility of the vaccine.
The Dengue Vaccine Initiative (DVI) is a consortium of the International Vaccine Institute, WHO, International Vaccine Access Center of the John Hopkins University Bloomberg School of Public Health, and Sabin Vaccine Institute laying the necessary groundwork for dengue vaccine decision-making and introduction in endemic countries.